NCT06080191

Brief Summary

This is a phase I, open label study to evaluate the safety, identify the recommended dose (RD) and obtain preliminar evidence of the efficacy of allogeneic, CD19-directed Chimeric Antigen Receptor T (alloCAR-T) cells in pediatric and young adults patients with relapsed/refractory B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL).

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at P25-P50 for phase_1

Timeline
183mo left

Started Apr 2024

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress12%
Apr 2024Jun 2041

First Submitted

Initial submission to the registry

September 12, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

October 12, 2023

Completed
7 months until next milestone

Study Start

First participant enrolled

April 28, 2024

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected
14.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2041

Last Updated

December 2, 2025

Status Verified

November 1, 2025

Enrollment Period

2.2 years

First QC Date

September 12, 2023

Last Update Submit

November 25, 2025

Conditions

B-cell Acute Lymphoblastic Leukemia

Keywords

B-cell acute lymphoblastic leukemiaChildrenAdolescentYoung adults

Outcome Measures

Primary Outcomes (1)

  • Safety and establishment of Dose limited Toxicity (DLT) of the infusion of CD19-CAR_Lenti_ALLO cells in pediatric and young adults patients affected by relapsed/refractory BCP-ALL in each dose level

    DLT is defined as any of the following events: (1) Grade III-IV GvHD refractory to first and second line treatment and chronic GvHD refractory to first and second-ine treatment; (2) any grade 4 non-hematologic toxicity; (3) grade 4 reactions realted to anti-alloCART infusion; (4) death related to alloCART infusion. The Maximum Tolerated Dose/Recommended Dose (MTD/RD) of CD19-CAR\_Lenti\_ALLO to be evaluated for efficacy in the phase II extension will be defined as the highest dose level at which \<33% of patients (no more than 1 out of 6) experience DLT.

    28 days

Secondary Outcomes (8)

  • To estimate the rate of occurrence of acute GvHD

    1 year

  • To estimate the severity of acute GvHD (according to the MAGIC criteria)

    1 year

  • To estimate the rate of occurrence of chronic GvHD

    1 year

  • To estimate the severity of chronic GvHD (according to the NIH 2014 criteria)

    1 year

  • To confirm the safety of the approach at the MTD/RD dose

    28 days

  • +3 more secondary outcomes

Study Arms (1)

Single arm

EXPERIMENTAL

A single IV infusion of CD19-CAR\_Lenti\_ALLO (allogeneic CD19-directed chimeric antigen receptor T-cells) on Day 0 after lymphodepletion. Patients will be divided in two cohorts based on donor HLA matching: cohort A (fully matched, familial or unrelated donor); cohort B (haploidentical donor). Patients will receive the following lymphodepletion: * Fludarabine (Flu) 30 mg/m2 per day on days -5, -4 and -3 * Cyclophosphamide (Cyclo) 1000 mg/m2 per day on days -5, -4 and -3. CD19-CAR\_Lenti\_ALLO will be infused at the following dose levels: Cohort A: * DL1: 3.0 x10\^6 CAR+ cells/kg * DL2: 5.0x10\^6 CAR+ cells/kg Cohort B: * DL1: 1x10\^6 CAR+ cells/kg * DL2: 3x10\^6 CAR + cells/kg If 2 DLT are observed in the dose level 1, an additional DL0 of 2.0x10\^6 CAR+ cells/kg (cohort A) or 0.5x10\^6 CAR+ cells/kg (cohort B) will be explored.

Drug: CD19-CAR_Lenti_ALLO

Interventions

CD19-CAR_Lenti_ALLODRUG

Biological/Vaccine: CD19-CAR\_Lenti\_ALLO A single infusion of CD19-CAR\_Lenti\_ALLO on Day 0

Single arm

Eligibility Criteria

Age1 Year - 35 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Patients with a diagnosis of CD19 expressing B ALL relapse, and one of the following:
  • Relapse after alloHSCT OR
  • Relapsed/refractory disease, with failure of frontline therapy and at least 2 rescue strategies, including CD19/CD22-directed monoclonal antibody and availability of a fully matched related donor.
  • CD19+ count ≥ 50 cells/mcl and/or Minimal Residual Disease (MRD) ≥ 10\^-4.
  • Voluntary informed consent. For subjects \< 18-years old their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.
  • Clinical performance status: patients \> 16 years of age: Karnofsky greater than or equal to 60%; patients ≤ 16 years of age: Lansky score than or equal to 60%.
  • Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for 4 months after receiving the lymphodepletion regimen.
  • Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.

You may not qualify if:

  • Pregnant or lactating women.
  • Severe, uncontrolled active intercurrent infections.
  • HIV, or active HCV and/or HBV infection.
  • Life-expectancy \< 6 weeks or rapidly progressive disease that in the evaluation of the investigator would compromise ability to complete study therapy.
  • Hepatic function: inadequate liver function defined as total bilirubin \> 4x upper limit of normal (ULN) or transaminase (ALT and AST) \> 6x ULN.
  • Renal function: serum creatinine \>3x ULN for age.
  • Blood oxygen saturation \< 90%.
  • Cardiac function: left ventricular ejection fraction lower than 45% by ECHO.
  • Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject.
  • Presence of active, grade 2-4 acute or chronic Graf versus Host Disease (GvHD) requiring steroid therapy or other immune-suppressive treatment.
  • Relapse occurring before 60 days after alloHSCT.
  • Concurrent or recent prior therapies, before infusion:
  • ii. systemic chemotherapy in the 2 weeks preceding infusion of CD19-CAR\_Lenti\_ALLO cells .
  • iii. anti-thymocyte globulin (ATG) or Alemtuzumab (Campath®)in the 8 weeks preceding infusion of CD19-CAR\_Lenti\_ALLO cells .
  • iv. immuno-suppressive agentis in the 2 weeks preceding infusion of CD19-CAR\_Lenti\_ALLO cells
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ospedale Pediatrico Bambino Gesù

Rome, Italy, 00165, Italy

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma

Condition Hierarchy (Ancestors)

Epstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Franco Locatelli, MD, PhD

    Director Department of Hematology/Oncology and Cell and Gene Therapy

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Franco Locatelli, MD, PhD

CONTACT

+39066859franco.locatelli@opbg.net

Francesca del Bufalo, MD, PhD

CONTACT

+39066859francesca.delbufalo@opbg.net

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 12, 2023

First Posted

October 12, 2023

Study Start

April 28, 2024

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 1, 2041

Last Updated

December 2, 2025

Record last verified: 2025-11

Locations

IT(1)